Intro To Clinical Sciences Flashcards
What is the suffix for neoplasms?
-oma
What is the definition of a neoplasm?
Lesion resulting from the autonomous abnormal growth of cells which persists after the initiating stimulus has been removed
Are neoplastic cells usually monoclonal or not?
Yes they are but once the neoplasm has started growing the cells won’t necessarily stay monoclonal.
What is the stroma of a neoplasm?
The support- connective tissue framework to provide mechanical support and nutrition
What cell and tissue types would you expect to find within a neoplasm’s stroma?
Fibroblasts, collagen, myofibroblasts and many blood vessels
What is angiogenesis?
Growth of new blood vessels
What factor determines the ability of a neoplasm to grow?
Presence of blood vessels
Can only grow to around 2mm whilst using diffusion only, past this size they need vascularisation
What are 6 features of benign neoplasm?
- Localised and non-invasive
- Slow growth rate in comparison to malignant so low mitotic activity
- Necrosis and ulceration are rare as they don’t outgrow their blood supply
- Close resemblance to normal tissue
- Circumscribed or encapsulated
- Often exophytic= up and out
What are 6 features of malignant neoplasms?
- Invasive- mastastases
- Rapid growth rate so high mitotic activity
- Variable resemblance to normal tissue
- Poorly defined/irregular border
- Hyperchromatic (dark) nuclei
- Necrosis and ulceration common as outgrows blood supply
What is a papilloma?
Benign
Non-glandular
Non-secretory
Epithelium
Neoplasm
What is being described here:
Benign
Non-glandular
Non-secretory
Neoplasm
Papilloma
What is an adenoma?
Benign
Glandular or secretory
Epithelium
Neoplasm
What is being described here:
Benign
Glandular or secretory
Epithelium
Neoplasm
Adenoma
What is a carcinoma?
Malignant tumour of epithelial cells
What is being described here:
Malignant tumour of epithelial cells
Carcinoma
Name the benign connective tissue neoplasms for the following:
Adipocytes
Cartilage
Bone
Vascular
Striated muscle
Smooth muscle
Nerves
Lipoma
Chondroma
Osteoma
Angioma
Rhabdomyoma
Leiomyoma
Neuroma
What is the suffix for a malignant connective tissue neoplasm?
-sarcoma
What are the exceptions where -oma is malignant?
Melanoma
Mesothelioma
Lymphoma
What is the definition of Carcinogenesis?
Transformation of normal cells to (malignant) neoplastic cells through permanent genetic alterations or mutations- which are always multistep
What is the definition of oncogenesis?
Transformation to malignant or benign neoplastic cells
What is the definition of carcinogenic?
Cancer causing
What is the definition of oncogenic?
Tumour causing
What are 5 classes of carcinogens?
Chemical
Viral
Ionising & non-ionising radiation
Hormones, paracytes and mycotoxins
Miscellaneous
What are 4 examples of viral carcinogens?
HPV
Herpes virus 8
Hep B
Merkle cell polyomavirus
What are 8 host factors for cancer risk?
Ethnicity
Age
Sex
Sexual behaviours
Diet/exercise
Premalignant conditions (eg polyps)
Inherited predisposition
Trans-placental carcinogenesis
What is a latent interval?
The time between exposure to a carcinogen and the time the cancer “begins”
What are the main stages (as in titles- very brief) involved in the formation of an atherosclerotic plaque?
Initial lesion
Fatty streak
Plaque progression
If it is unstable the plaque may then rupture
Which cells produce collagen in fibrous scarring?
Fibroblasts
Give examples of where granulomatous inflammation occurs (where collection of macrophages surrounds lymphocytes)
May be due to a myobacterial infection such as TB or leprosy
Seen in chron’s and sarcoidosis
Which 4 main cells are seen in inflammation?
Neutrophil polymorphs
Macrophages
Lymphocytes
Fibroblasts
Which cell is being described:
White blood cell made in bone marrow
Short lifespan of 2-3 days
Polyobed nucleus
Eat debris and bacteria
Contain lysosomes
Neutrophil polymorph
Which cell is being described:
White blood cell
Long lifespan (months-years)
Phagocytose debris and bacteria
Antigen presenting cells- secondary immune response
Macrophages
Which cell is being described:
Long-lived, for years
Control inflammation and antibodies
Immunological memory cell
Lymphocyte
What is the sequence of acute inflammation?
- Injury/infection
- neutrophils arrive, phagocytose and release enzymes
- macrophages arrive and phagocytose
- resolution with clearance/ progress to chronic
What are 3 examples of acute inflammation and what is another name for it?
= neutrophil-mediated
Acute appendicitis
Frostbite
Streotococcal sore throat
What is the sequence of chronic inflammation and what can it also be called?
= macrophage/lymphocyte mediated
Either progresses from acute of starts as ‘chronic’
Starts with macrophages and lymphocytes then usually fibroblasts
If there is no tissue damage then it can be resolved but often ends up with repair and formation of scar tissue
How would you treat inflammation if you wanted to?
Ice- stops capillaries from being flooded with blood and fluid escaping
Antihistamine- histamine is a chemical mediator of acute inflammation
Ibuprofen- inhibits prostaglandin sythetase
Steroids- upregulate inhibitors of inflammation, downregulates mediators
Which of the following tumours never metastasises?
• Malignant melanoma
• Small cell carcinoma of the lung
• Basal cell carcinoma of the skin
• Breast cancer
Basal cell carcinoma
Which of the following tumours does not commonly metastasise to bone?
• Breast cancer
• Lung cancer
• Prostate cancer
• Liposarcoma
Liposarcoma
Those that do are breast, lung, prostate, renal cell and thyroid
What is the name of malignant tumour of striated muscle?
Rhabdomyosarcoma
What term describes a cancer that has not invaded through the basement membrane?
Carcinoma in situ
What is the name of a benign tumour of glandular epithelium?
Adenoma
Which of these tumours does not have a screening programme in the UK?
• Breast
• Colorectal
• Cervical
• Lung
Lung
What is the name of benign tumour of fat cells?
Lipoma
What is the name of a malignant tumour of glandular epithelium?
adenocarcinoma
Which of the following is not a feature of malignant tumours?
• vascular invasion
• Metastasis
• Increased cell division
• Growth related to overall body growth
Growth related to overall body growth
A transitional cell carcinoma of the bladder is a malignant tumour?
• True
• False
True
A leiomyoma is a benign tumour of smooth muscle?
• True
• False
True
Radon gas is a cause of lung cancer?
• True
• False
True
Which tumour has the shortest median survival?
• Basal cell carcinoma
• Malignant melanoma
• Breast cancer
• Anaplastic carcinoma of the thyroid
Anaplastic carcinoma of the thyroid
Ovarian cancer commonly spreads in the peritoneum?
• True
• False
True
What are reasons for an autopsy?
Cause of death not known
Presumed iatrogenic
Anaesthetic deaths
Abortion
Complications of therapy
Presumed unnatural
Suicide (by legal diagnosis)
Unlawful killing
Neglect
Custody deaths
War
Industrial deaths
What is apoptosis?
Programmed cell death in normal cell turnover
How does apoptosis occur?
P53 protein detects DNA damage and triggers apoptosis if appt.
Enzymes are released which auto digest the cell (many of these enzymes = caspases)
In which diseases is apoptosis relevant?
Cancer- cells often don’t apoptose, sometimes due to mutation in p53 gene so can no longer detect damage
HIV- HIV can induce apoptosis (in CD4 helper cells)
What is necrosis?
Wholesale destruction of large numbers of cells by some external factor
What are 4 clinical examples of necrosis?
- Infarction due to loss of blood supply
- Frostbite
- Toxic venom from reptiles and insects
- Pacreatitis
Define hypertrophy:
Increase in size of an organ due to increase in the size of its constituent cells
Define hyperplasia:
Increase in size of an organ due to increase in the number of its constituent cells
Where do hypertrophy and hyperplasia occur:
Hypertrophy= in organs where cells cannot divide
Hyperplasia= in organs where cells can divide
Mixed hypertrophy/hyperplasia occurs in organs where cells can divide
What is an example of mixed hypertrophy/hyperplasia?
Smooth muscle cells of the uterus during pregnancy
Define atrophy:
Decrease in size of an organ due to decrease in size and/or number of its constituent cells
Define metaplasia:
Change in cell differentiation from one fully-differentiated type to another fully-differentiated type (usually caused by consistent change in environment)
What is one example of metaplasia?
Barrett’s oesophagus
Oesophageal squamous epithelium to glandular epithelium in continued acid reflux from the stomach
Define dysplasia:
=abnormal growth
Morphological change that may be seen in cells in the progression on to development of cancer (neoplasia)
What is an example of dysplasia?
Bronchial epithelium in cigarette smokers- metaplasia from ciliated to squamous
What are the two types of bone metastases?
Sclerotic (increases BMD)
Lytic (reduced BMD)
What are 4 tumour which commonly metastasise to the liver?
Colon
Stomach
Pancreas
Carcinoid tumours of intestine
Why do many tumours metastasise to the lung?
Because the metastases become lodged in the small pulmonary vessels
The lungs act like a filter for tumours
Why is tumour angiogenesis important?
Because tumours cannot grow above ~2mm when they have no blood supply
If we can find a way to stop angiogenesis- we can find a way to stop tumours growing?
What are 3 factors that allow extravasation of tumour cells?
Adhesion receptors
Collagenases
Cell motility
What is the role of matrix metalloprotinases in cancer?
These are produced to help the cancer metabolise collagen and the basement membrane
• Which of these is an example of acute inflammation:
◦ Glandular fever
◦ Leprosy
◦ Appendicitis
◦ Tuberculosis
Appendicities
In which of the following does granulomatous inflammation occur: =helpful clinical presentation of collection of macrophages surrounded by lymphocytes
◦ Chron’s
◦ Acute appendicitis
◦ Infectious mononucleosis
◦ Lobar pneumonia
Chron’s
• Which of the following is a chronic inflammatory process from its start:
◦ Appendicitis
◦ Cholecystisis
◦ Infection mononuleosis
◦ Lobar pneumonia
Infection mononucleosis
= mono = glandular fever
• Which of the following is an example of hyperplasia:
◦ Bodybuilder’s biceps
◦ Enlarged left ventricle
◦ Benign prostate enlargement
◦ Wasting of quads after immobilisation
Benign prostate enlargement
• Which is not an example of apoptosis:
◦ Loss of cells from tips of duodenal villi
◦ Loss of cells during embryogenesis
◦ Renal infarction
◦ Graft versus host disease
Renal infarction
= necrosis
• Which is an example of atrophy:
◦ Biceps of bodybuilder
◦ Uterus in pregnancy
◦ Brain in dementia
◦ Prostate in older age
Brain in dementia
What two factors mean that blood clots are rare?
Laminar flow= cells travels in the centre of vessels not touching the sides
Endothelial cells lining vessels are not ‘sticky’ until they are damaged
Define thrombosis:
The formation of a solid mass from blood constituents in an intact vessel in a living person
What are the 3 ‘causes’ of thrombosis?
Change in vessel wall
Change in blood constituents
Change in blood flow
Define embolus:
Mass of material in the vascular system able to become lodged within a vessel and block it
What can an embolus be?
Most commonly a thrombus
Sometimes air, cholesterol crystals, tumours and fat
Define ischaemia:
Reduction in blood flow to a tissue without any other complications
Define infarction:
Reduction in blood flow to a tissue that is so reduced it can no loner support the mere maintenance of cells in the tissue so they die
Define congenital:
Present at birth- can be inherited or environmental
What 2 cell types don’t regenerate?
Myocardial cells
Neurones
What is the difference between resolution and repair?
Resolution= initiating factor removed and tissue left undamaged or able to regenerate
Repair= initiating factor is still present and tissue left damaged or unable to regenerate
What is healing by primary and secondary intention?
Primary intention- when wound edges are clean, surgically incised, without much loss of cell/tissue and wounds have opposed edges
Secondary intention- wound edges are not clean, margins are irregular, and not surgically incised
Are the following examples of repair or resolution?
Heart after myocardial infarction
Brain after cerebral infarction
Spinal cord after trauma
Repair
When a bone is fractured and kept stable what is happening- resolution or repair?
Resolution
When a bone is fractured and NOT kept stable what is happening- resolution or repair?
Repair
What is atherosclerosis?
Accumulation of fibrolipid plaques in systemic arteries
What are the 4 main risk factors for atherosclerosis?
Hypertension
Hyperlipidaemia
Cigarette smoking
Poorly-controlled diabetes
What is the current theory behind atherosclerosis?
Endothelial cells are delicate- can be damaged by smoking, lipids, oxidative agents etc.
Damage leads to endothelial ulceration, microthrombi, eventual development of established atherosclerotic plaques.
Give the process of atherosclerotic plaque formation:
- Damage to endothelium- becomes permeable to LDLs
- LDLs deposit in tunica intima and become oxidised- now they can’t leave
- Oxidised LDLs activate endothelial expressions for WBCs so monocytes are taken into intima
- Monocytes -> macrophages + LDL = FOAM
- FOAM release lipids when they die= plaque
What are the main ‘types’ of drugs?
Enzyme
Ligand
Transporter
Channel
What are the types of ligands?
Exogenous (drugs)
Endogenous (hormones, neurotransmitter)
What are the 4 types of receptors?
Ligand-gated ion channels (nicotine, ACh)
G protein coupled receptors, GCPR (beta-andrenoceptors)
Kinase-linked receptors (growth factors)
Cytosolic/nuclear receptors (steroid)
What controls the activity of g-protein coupled receptors?
Regulated by factors that control their ability to bind to and hydrolyze GTP to GDP
For the following receptors, what are their G proteins, couples and 2nd messengers?
M3R
B2-AR
M3R: Gq protein, PLC couple, IP3/DAG 2nd mes.
B2-AR: Gs protein, AC couple, cyclic AMP 2nd mes.
How do kinase-linked receptors work?
Kinases are enzymes which catalyse the transfer of phosphate groups between proteins- substrate gains phophate from ATP
Receptors are activated when the binding of an extracellular ligand causes enzymatic activity on the intracellular side
How to nuclear receptors work?
By modifying gene transcription
What is a drug’s intrinsic activity?
The ability of a drug-receptor complex to produce a maximum functional response
What is a drug’s potency?
The response given by a drug at a given dose
What is the efficacy of a drug?
How ‘much’ it works- ie. Does it give a 100% response at a given dose
What is competitive vs non-competitive antagonism?
When two drugs have opposing effects.
In competitive they bind to the same site
In non-competitive the antagonist binds to an allosteric site.
What are the receptor-related and tissue-related factors that govern drug action?
Receptor-related: affinity and efficacy
Tissue related: receptor number and signal amplification
What is drug affinity?
How well the ligand binds to the receptor
What is efficacy of ligands?
How well the ligand activated the receptor
What is the affinity and efficacy of agonists and antagonists?
Agonists have both affinity and efficacy- some more than others.
Antagonists have affinity and ZERO efficacy
What is bromacetyl alprenolol menthan (BAAM)?
An irreversible antagonist- once bound to the receptor, it will not com off
What is the receptor reserve?
When a response is seen when not all receptors have been stimulated so there are spare receptors even though a response is seen
What are two pathological examples of where there is an imbalance of chemicals and receptors?
In allergies where there is too much histamine
In Parkinson’s where there is too little dopamine
What are agonistic and antagonistic ligands?
Agonists activate a receptor when bound
Antagonists reduce the effect of a receptor when bound
What is inverse agonism?
When a drug that binds to the same receptor as an agonist induces a response opposite to that of the agonist.
What is drug tolerance?
When there is a reduction in the effect of the agonist over time often when there are continuously high concentrations
What is drug desensitisation?
The rapid desensitisation to a drug which is uncoupled, internalised and degraded
What are isoprenaline and salbutmaol?
Isoprenaline is a non-selective B-adrenoceptor agonist.
Salbutamol is selective- will only activate the receptors in the lungs where as Iso is non-specific
Define physicochemical:
How two drugs interact independent of the body- so the way they interact has nothing to do with any body systems or environments.
Define pharmacodynamics:
The effect a drug has on the body
(Not always the primary effect)
Define pharmacokinetics:
What the body does to the drug.
How a drug is absorbed, distributed, metabolised and excreted.
What are the 4 types of pharmacodynamic drug interactions?
Summation/additive
Synergism
Antagonism/blockade
Potentiation
What is summative/additive pharmacodynamic drug interaction?
When two drugs work together to do the same thing and have an effect equal to the sum of their individual effects.
What is synergistic pharmacodynamic drug interaction?
When two drugs work together to produce a response greater than the sum of both individual responses
What is antagonistic/blockage pharmacodynamic drug interaction?
When one drug antagonises/blocks the effect of another so 1+1=0
What is Potentiation pharmacodynamics in drug interactions?
When one drug makes the effect of another more potent without changing itself.
What is pharmacokinetics ADME?
A- absorption
D- distribution
M- metabolism
E- excretion
Most drugs are hepatically metabolised and renally excreted
What is bioavailability?
How available a drug is over time (use area under graph of blood concentration x time)
Fraction of an administered drug that reaches the systemic circulation
Why would acidity affect drug absorption?
Because all drugs exist in an equilibrium of their ionised and unionised states- where the unionised drugs can move into cells though the bilayer.
PH affects the equilibrium and therefore how much drug can pas into the cells
What is enzyme induction and inhibition in pharmokinetics?
How some drugs up or down regulate the enzymatic change of a drug into its active form therefore up or down regulating the active drug
Give 2 examples where you should remember drug interactions?
Warfarin (in context of protein binding and enzyme inhibition/induction)
And any that may induce acute kidney injury (ace inhibitors, NSAIDs, furosemide and gentimicin)
What are the two categories of cholinergic receptors?
Nicotinic and muscuarinic
What do statins do chemically?
Block the rate limiting step in the cholesterol pathway- reduces levels of “bad cholesterol”
What are 4 ways in which enzyme inhibitors can be used to treat Parkinson’s?
Carbidopa inhibitor for DDC (L-dopa -> dopamine)
Tolcapone inhibitor for COMT (L-dopa -> 3-methyl DOPA) both in periphery and in CNS
Selegiline inhibitor for MAO-B (dopamine -> DOPAC)
What are the 3 main types of protein ports in cell membranes, and what are they?
Uniporters= use energy from ATP to pull molecules in
Symporters= use the movement in of molecules to pull in another molecule against a concentration gradient
Antiporters = one substance moves against its gradient using energy from a second substance moving with its gradient
How does furosemide target NKCC?
It inhibits trasport in NKCC (sodium potassium chlorine cotransported).
= a diuretic so inhibits
What would we see if epithelial (sodium ) channel failed?
Heart failure
What would we see if voltage-gated channel failed?
Nerve failure and arrhythmia
What would we see if metabolic (potassium) channel failed?
Diabetes
What would we see if receptor activated (chloride) channel failed?
Epilepsy
What does heterotrimeric mean?
Has two sets of three independent proteins- multiple genes code for different sub-units
What channels are blocked by high affinity diuretics?
ENaC= epithelial sodium channels
Where are voltage gated calcium channels found?
Often at excitable cells such as muscle and neurones
How are voltage-gated calcium channels opened?
They are normally found closed, but are activated at depolarised membrane potentials- Ca2+ enters the cell and the Ca-sensitive K channels are opened …
What channel does amlopdipine work on?
Voltage gated calcium channels- inhibits contraction of cardiac muscle
Causes vasodilation to lower blood pressure
What channels does lidocaine affect and what does it do?
Lidocaine= anaesthetic
It blocks transmission of action potential to voltage gated sodium channels
What are the 3 conformational states of voltage gated channels?
Closed
Open
Inactivated
What is one place where voltage gated K channels are important?
Regulation of insulin in the pancreas- increased glucose leads to block of these channels and opening of Ca2+ channels so insulin release is triggered
Where/ how do repaglinide, nateglinide and sulfonylyureal all act?
On voltage gated K channels- block them so insulin is secreted
So used to treat type 2 diabetes
Where/how does digoxin act?
On the Na/K ATPase- mainly in the myocardium
Used for atrial fibrillation and heart failure
Inhibition causes an increase in intracellular Na so there is decreased activity in Na-Ca exchanger and hence less Ca in intracellularly
Slows down action potential therefore slows down heart rate
What is the proton pump : K/H ATP-ases targeted for the treatment of?
This is the proton pump of the stomach and is responsible for the acidification of the stomach so inhibition of this inhibits acid secretion
What does omeprazole target?
Proton pumps in the stomach to lower stomach pH
What are 3 non-medical examples of irreversible enzyme inhibitors?
Nerve gases (sarin)
Insecticides
Pesticides
What are 5 drugs that are irreversible enzyme inhibitors?
Omeprazole (proton pump inhibitor)
Ramiprill (ACE inhibitor)
Aspirin (COX inhibitor)
Paracetamol (COX inhibitor)
Simvastatin (statin)
What does xenobiotic mean?
Compound foreign to an organism’s normal biochemistry eg any drug or poison
What are cytochrome P450s and what do they do?
Primarily membrane associated monoocidase proteins in the mitochondria/ER
They are major enzymes of drug metabolism
Most drugs undergo deactivation by CYPs, some are activated to their active compounds
What are the naturally occurring opioids?
Morphine
Codeine
What are the simply chemically modified opioids?
Diamorphine
Oxycodone
Dihydrocodeine
What are the 4 synthetic opioids?
Pethidine
Fentanyl
Alfentanil
Remifentail
What are opioid’s synthetic partial agonist and antagonist?
Synthetic partial agonist: buprenorphine
Antagonists: naloxone
How much oral morphine is metabolised by first pass metabolism in the liver?
50%
With morphine, what would the equivalent intramuscular or IV dose be for 10mg of oral morphine?
5mg
50% of oral is metabolised by liver
What are 4 routes of administration for morphine?
Paranteral (not oral)- IM, IV, subcutaneous
IV patient controlled analgesia
Epidural/CSF
Trans-dermal patches for lipid soluble drugs eg fentanyl
Which is more potent and faster acting, morphine or diamorphine?
Diamorphine
What is heroin?
Diamorphine
How do opioids work?
Inhibit the release of pain transmitters at the spinal cord and midbrain giving euphoria- changes the emotional perception of pain
Act on g-protein coupled receptors via second messenger
Why are opioids addictive?
They act on the descending inhibition of pain- part of fight or flight
These were never designed for sustained activation (which opioids provide) and sustained activation leads to tolerance and addiction
What are the 4 opioid receptors?
Mu (MOP)
Delta (DOP)
Kappa (KOP)
Nociceptin (NOP)
Why do we use MOP agonists instead of KOP agonists?
MOP agonists cause depression instead of euphoria
What are the relative potencies of diamorphine, morphine and pethidine?
5
10
100
What is the difference between dependence and tolerance?
Tolerance is the down regulation of receptors that occurs with prolonged use of a drug- where you then need a higher dose to achieve the same effect
Dependence is the psychological effects- craving, euphoria etc
What are the timings of opioid withdrawal?
Starts within 24 hours and lasts around 72
What are 7 side effect of opioids?
Respiratory depression
Sedation
Nausea and vomiting
Constipation
Itching
Immune suppression
Endocrine effects
What do you do if someone is experiencing opioid induced respiratory depression?
ABC (+ 999)
Naloxone
IV- titration to effect- 1ml in 10ml saline- don’t give it all at once
What is opioid induced respiratory depression?
Combination of opioid-induced central respiratory depression (reduced respiratory drive), decreased level of consciousness and upper airway obstruction due to decrease in supraglottic airway tone.
For what reason were opioids heavily marketed n the US in the 90s?
For treatment of chronic non-cancer pain
Why do we need to be aware of CYP2D6 in individuals taking codeine?
Codeine is metabolised by CYP2D6
It’s activity is decreased n=in 10-15% of Caucasian population and absent in a further 10%- in these people codeine will have a reduced or absent effect
CYP2D6 is overactive in 5% of this population so these may be at risk of respiratory depression with codeiene
How is morphine metabolised?
To morphine 6 glucuronide which is more potent than morphine and is renally excreted
What is tramadol, how is it metabolised?
A weak opioid agonist- slightly stronger than codeine
Is metabolised by CYP2D6 to o-desmethyl tramadol to be active- therefore won’t be effective in about 10% of people
Why do we need to think about how tramadol interacts with certain drugs?
It has effects as a serotonin and nor-epinephrine reuptake inhibitor
It interacts with SSRIs, tricyclic antidepressants and MAOIs
What are the features of type 1 hypersensitivity reactions?
= allergy
Antigen reacts with IgE bound to mast cell
Eg. Anaphylaxis
What are the features of type 2 hypersensitivity reactions?
IgG or IgM binds to antigen on cell surface
Antibody mediated immune response
Eg. Pernicious anaemia, rheumatic fever
What are the features of type 3 hypersensitivity reactions?
Free antigen and antibody combine (IgG, IgA) to form immune complex
Eg. Systemic lupus erythematosus
What are the features of type 4 hypersensitivity reactions?
=T-cell mediated
=Delayed type hypersensitivity
Cell dependant (Th1/cytotoxic T cells/macrophages)
Divided into 3 subgroups: damage caused activation of macrophages, activation of TH2 cells and directly by cytotoxic T cells
Eg. Tuberculosis
What are examples of hypersensitivity reactions for types 1-4?
1: allergy, asthma, anaphylaxis
2: some drug allergies eg penicillin
3: serum sickness, contact dermititis
4: chronic asthma, contact dermititis
What are the clinical presentations of allergy in skin, airways, GI and anaphylaxis?
Skin: swelling, itching and red
Airways: excessive mucus production, bronchoconstriction
GI: abdominal bloating, vomiting, diarrhoea
Anaphylaxis: airways, breathing, circulation etc.
What are allergies?
Abnormal responses to harmless foreign materials
What are the 7 allergic diseases?
Anaphylaxis
Allergic asthma
Allergic rhinitis (hay fever)
Atopic dermatitis
Oral allergy syndrome (food allergy)
Angiodema (not idiopathic one)
What are the 3 main mediators of allergy?
Cytokines
Chemokines
Lipids
What are the 3 main cells of allergy?
Mast cells
Eosinophils
Basophils
What is the average serum concentration of IgE?
0.3-100 micrograms/ml
What is the difference/similarities between eosinophils and basophils?
Eosinophils respond in parasitic infections. They have an antagonistic action to basophils and have IgE receptors
Basophils are involved in inflammatory reactions= the circulating form of MAST cells. They also have receptors for IgE and release histamine
How are mast cells developed and what are they characterised by?
Produced by a specific cell lineage in marrow
Characterised by a requirement for c-kit protein (systemic mastocytosis= caused by c-kit mutations)
What proteins binds to IgE?
FceRI = high affinity
FceRII= low affinity
CD23= low affinity
Which 6 cells express FceRII and CD23 and what is their function in this context?
B cells, T cells, monocytes, eosinophils, platelets and neutrophils
Their functions are to regulate IgE synthesis, trigger cytokines release by monocytes and to present antigens
What are the 3 main cells that express FceRI?
Eosinophils
Mast cells
Basophils
What is the immediate response from mast cells?
They have preformed compounds:
Histamine (arteriolar dilation, capillary leakage and cholinergic reflex bronchoconstriction)
Chemotactic factors (cytokines)
Proteases (tryptase, chymase)
Proteoglycans (chondroitin sulphate and heparin)
Most of these factors lead to eosinophil attraction and activation
What are the responses of Mast cells within minutes and within hours?
Within minutes they release lipid derived mediators:
Leukotrienes (endothelial contraction with vascular leakage), prostaglandin D2 (inducer of smooth muscle contraction), platelet activating factor (increased platelet aggregation).
Within hours they release cytokines IL-8, IL-5, IL-4, IL-14 and RANTES
What are direct activators of mast cells?
Cold/mechanical deformation (Asthma?)
Aspirin
Tartrazine
NO2
Latex
What are indirect activators of Mast cells?
Indirect because they act via IgE
Allergens such as latex, venom, foods, drugs, dander- for these prior sensitisation is required
Bacterial viral antigens
What are the roles of the following cells in allergy:
Lymphocytes
Dendritic cells
Neurons
Lymphocytes (th2)
Dendritic cells (for antigen presentation)
Neurons (cholinergic/andrenergic)
What are 4 features of asthma?
Complex inflammatory disease of the bronchi
Commonly triggered by allergens
Can involve eosinophil influx to the lungs
Often involves IgE
What is atopy?
A hereditary predisposition to the development of immediate hypersensitivity reactions against common environmental antigens
What are 3 features of chronic asthma?
Non-Th2 cell mechanism
CD8 T cells control eosinophil responses
Similar to type 4 hypersensitivuty
How can we use desensitisation in allergy treatment?
= immunotherapy
Increasing doses of antigen sub-lingually or sub-cutaenously
There are risks of moderate and life-threatening reactions
How can we use IgE prevention to treat allergies?
Can we supress Th2?
Can we deliver suppressive cytokines?
We can use anti-DC23 antibodies to decrease IgE levels
What is one example of anti-IgE therapy and what are the downsides to it?
Xolair (selectively binds to IgE)
= inhibits the binding of IgE to FceRI
It is very costly, slightly increases cancer incidence
What are 6 treatment strategies for allergy?
Avoid allergens
Desensitisation to allergens
Prevent IgE production
Prevent IgE interaction with receptor
Prevent mast cell activation
Inhibit mast cell products
What are the 4 main anti-cytokine antibodies?
IL-5 antibody= mepolizumab
IL-5 receptor antibody= reslizumab, benralizumab
Anti IL-4/IL-13 = depilumab
What are 5 ways in which we can reduce mast cell activation to treat allergies?
Mast cell stabilisers
Beta2 agonists (increase cAMP)
Glucocorticoids (inhibit gene transcription)
Calcium channel blockers
Signalling inhibitors
What are the ways in which we can inhibit mast cell products to treat allergy?
Histamine receptor agonists
Leukotriene antagonists
Tryptase inhibitors (prevent airway smooth muscle activation)
Protease-activated receptor 2 agonists (PAR-2 agonists)
What are the 3 main stages of drug development?
Drug discovery
Preclinical development
Clinical development
What are the medications derived from the foxglove plant?
Digitalis
What are the medications derived from poppies?
Morphine
What are the medications derived from deadly nightshade?
Atropine
What are the medications derived from periwinkle?
Vincristine
What are three approaches to neutralisation of tumour necrosis factor a?
Chimeric antibody (infliximab)
Fusion protein (etanercept)
Human antibody (adalimumab)
What are the features of infliximab? (Derivative, use etc)
It is a monoclonal antibody from mice against TNF alpha
Initially used for chron’s disease now for rheumatoid arthritis also
Given by IV infusion every 6-8 weeks
What is adalimumab (humira)
HUman Monoclonal antibody In Rheumatoid Arthritis
Define adverse drug reaction:
Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug
What is the difference between adverse drug reaction and side effects?
Side effects can be beneficial but adverse drug reaction are ALWAYS negative
What are the 3 types of adverse drug reaction?
Toxic effects (when beyond the therapeutic range)
Collateral effects (when within the therapeutic range)
Hyper-susceptibility effects (when below the therapeutic range)
What are two reasons a toxic adverse drug effect may occur?
If dose is too high
If excretion is impaired
What are the ~7 patient risk factors for adverse drug reactions?
More common in women
More common at extreme ages (old and young)
Polypharmacy
Genetic predisposition
Hypersensitivity
Hepatic/renal impairment
Adherence problems
What are the drug risk factors for adverse drug reactions?
Low therapeutic index (easy to reach toxic range)
Steep dose-response curve
What are the 7 causes of adverse drug reactions?
Pharmaceutical variation
Receptor abnormality
Abnormal biological system that is unmasked by the drug
Abnormalities in drug metabolism
Immunilogical
Drug-drug interactions
Multifactorial
What are the 6 time dependent adverse drug reactions?
Rapid reactions (eg due to quick histamine release with rapid administration of vancomycin)
First dose reactions
Early reactions
Intermediate reactions
Late reaction (maybe when drug is stopped)
Delayed reactions (thalidomide in pregnancy)
Give the Rawlins Thompson classification:
Type A = Augmented pharmacological
Type B = Bizarre or idiosyncratic
Type C = Chronic
Type D = Delayed
Type E = End of treatment
Type F = Failure of therapy
Give the features of type A drug reactions:
= augmented
Predictable, dose dependent, common
Excludes drug abuse and overdose
Give the features of type B drug reactions:
= bizarre
Not predictable, not dose dependent
Eg. Anaphylaxis from penicillin
Less common but more often serious
Can be allergy or hypersensitivity
Give the features of type C drug reactions:
= chronic
Eg. Osteoporosis from long term steroids
Uncommon and related to cumulative dose
Give the features of type D drug reactions:
= delayed
Eg malignancies after immunosuppression
Usually dose related and uncommon
Give the features of type E drug reactions:
= end of treatment
May occur after abrupt drug withdrawal eg. Opiate withdrawal syndrome
Give the features of type F drug reactions:
= failure
Eg. Getting pregnant on the pill because taking other antibiotics
What is DoTS in the context of adverse drug reactions?
Dose relatedness
Timing
patient Susceptibility
What are 4 things to look out for if an adverse drug reaction is suspected?
Symptoms soon after new drug is started
Symptoms after dosage increase
Symptoms disappear when drug is stopped
Symptoms reappear when drug is restarted
What are the 7 most common drugs to have ADRs?
Antibiotics
Anti-neoplastics
Cardiovascular drugs
Hypoglycaemics
NSAIDs
CNS drugs
What is the yellow card scheme?
A scheme to report ADRs
These only need to be suspected
It is voluntary
What do you report on a yellow card?
All suspected reactions for herbal medicine
All suspected reactions for black triangle drugs (undergoing observation even though they’re on the market)
All serious suspected reactions for established drugs, vaccines and drug interactions
What is the black triangle?
Used to indicate medicine that are undergoing additional monitoring
What 4 pieces of information needed to be included on a yellow card?
Suspected drug(s)
Suspected reaction(s)
Patient details
Reporter details
What are examples of immediate and delayed drug hypersensitivity?
Immediate- urticarial (rash), anaphylaxis
Delayed- hepatitis, other rashes
Which type of hypersensitivity is anaphylaxis?
Type 1
What are the features of type 1 hypersensitivity- anaphylaxis?
Had a prior exposure
IgE antibodies formed after exposure
IgE becomes attaches to mast cells
Re-exposure causes mast cell degranulation and release of substances such as histamine
What is non immune anaphylaxis?
Due to direct mast cell degranulation
No prior exposure necessary
Clinically identical to immune anaphylaxis
What are the main features of anaphylaxis?
Immediate rapid onset after exposure to drug (80-90%)
Swelling of lipids, face, oedema
HYPOtension
Cardiac arrest
How do we manage anaphylaxis?
Basic life support
Stop drug if possible
Adrenaline (Intramuscular- epi-pen is 300mcg, hospital is 500mcg)
High flow oxygen
Antihistamines if rash
How does adrenaline treat anaphylaxis?
Causes vasoconstriction
Stimulates beta1-adrenoceptors
Reduces oedema
Bronchodilates
Attenuates further release of mediators from mast cells and basophils by nincrease c-AMP so release of inflammatory mediators is reduced
What is the clinical criteria of a drug allergy?
Does not correlate with pharmacological properties of the drug
No linear relation to dose
Reaction similar to other allergens
Disappearance on cessation and reappearance on re-exposure
Only occurs in a minority of patients on the drug
What is a confirmatory blood test for anaphylaxis?
Serum mast cell tryptase.
Peaks an hour after reaction and lasts around 6 hours
How does adrenaline treat anaphylaxis?
Has beta-adrenergic receptor activity.
Stimulation of beta1-adrenergic receptors causes positive ionotropic and chonotropic effects on the heart (increased force and rate).
Stimulation of beta2-adrenergic receptors reduce oedema and bronchodilates
What occurs when histamine receptors are stimulated?
Histamine 1 receptors mediate vasodilation, hypotension and flushing.
Histamine 2 receptors increase atrial and ventricular contractility, atrial chronotrophy and coronary artery vasodilation.
Why may leukaemia cause splenomagely?
Because the spleen removes RBCs
Define innate immune response:
Non-specific defence system that you were born with
Define adaptive immune response:
Acquired defence to destroy/prevent growth of pathogens
What are the 6 cells of the innate immune system?
Neutrophils
Natural killer cells
Macrophages
Mast cells
Eosinophils
Basophils
Briefly explain the role of neutrophils:
Most abundant WBC, phagocytic and involved in inflammation
Briefly explain the role of macrophages:
(When monocytes migrate from blood to tissue they become macrophages)
Phagocytic, antigen presenting and secrete cytokines
Briefly explain the role of basophils:
Involved in allergies
Briefly explain the role of eosinophils:
Involved in parasitic infections
Briefly explain the role of mast cells:
Involved in anaphylaxis and asthma (IgE binds to allergen which then binds to mast cells causing them to release products incl histamines)
Briefly explain the role of natural killer cells:
Release Lytic granules that kill cells infected with virus
What are the main antigen presenting cells?
Dendritic cells§
What are the cells of the adaptive immune system?
T cells: T helper cells and cytotoxic T cells
B cells
What proteins do the different types of T cell present?
T helper cells: CD4
Cytotoxic T cells: CD8
What is the role of T helper cells?
Express CD4
Activate B cells and cytotoxic T cells
What is the role of cytotoxic T cels?
Express CD8
Release perforin that cause cells to lyse
What is CD20 and what’s its significance?
The mature B cell marker (protein on B cells)
Monoclonal antibodies targed CD20
Used to measure levels of B cells which may be elevated in certain B cell leukaemias
What are the 3 main roles of antibodies?
Neutralise toxins
Opsonisation of pathogens (attract phagocytes to them)
Destroy pathogens
What are the 4 main types of antibody?
IgA
IgM
IgG
IgE
What are the functions and features of antibody IgG?
It is the most abundant antibody in the blood and is highly specific
It has 4 subclasses
It can cross the placenta
What are the functions and features of antibody IgE?
It is bound to mast cells and basophils by FceR.
Important in allergy and parasite infections.
Out of IgG and IgM, whose levels increase more in a second exposure and whose increase the same as the first exposure?
IgG levels increase in second exposure
IgM levels experience the same increase as in the first exposure.
(Should be IgMore but it’s not!)
What is active vs passive immunity?
Active: immunity produced by the host immune system
Passive: immunity produced with no host participation
What are the 3 steps of acute inflammation?
- Vascular component (dilation of vessels and increased vascular permeability)
- Exudative component (leakage of protein rich fluid)
- Neutrophil polymorph (recruited to tissue)
What are the 4 stages to neutrophil polymorph recruitment in acute inflammation?
- Migration (increased plasma viscosity and slowing flow causes neutrophils to migrate to plasmatic zone)
- Adhesion (adhesion of neutrophils to endothelium within venules)
- Emigration (neutrophils pass through endothelial cells to the basal lamina and then vessel wall)
Diapedesis (some RBCs may also escape from vessels = passive transport)
Name 6 possible causes of acute inflammation:
Microbial infection (bacteria, virus)
Hypersensitivity reactions
Physical agents (trauma, heat)
Chemicals
Bacterial toxins
Tissue necrosis
Name 5 ways in which acute inflammation may appear clinically:
Rubor (Redness due to small vessel dilation)
Calor (heat peripherally)
Tumour (swelling due to oedema or mass)
Dolor (=pain)
Loss of function (due to ischaemia?)
What are 4 possible outcomes of acute inflammation?
- Resolution
- Suppuration (formation of pus -> scarring)
- Organisation (Replacement by granulation tissue)
- Progression to chronic
Define cholinergic and andrenergic:
Cholinergic= relating to acetylcholine (ACh) and its receptor
Adrenergic= relating to (nor)adrenaline and their receptors
Define commensal:
Organism which colonises (lives in) the host but causes no disease in normal circumastances
(If these move to somewhere they don’t belong they can then cause disease eg UTI)
What is an opportunist pathogen?
Microbe that only causes disease if host defence are compromised- normally don’t cause disease
Define virulence/pathogenicity:
The degree to which a given organism is pathogenic
What colour do gram positive and negative bacteria stain with gram stain?
Gram positive = purple
Gram negative = red
What in bacteria structure allows adhesion to human cells?
Pili/fimbriae
What type of bacteria do not stain with gram stain?
Mycobacteria
How can we classify mycobacteria?
Ziehl-Neelsen stain
How do gram positive and negative bacteria differ structurally?
Gram positives have: capsule, large peptidoglycan layer then an inner membrane
Gram negatives: capsule, lipopolysaccharide layer (endotoxin), outer membrane, lipoproteins, small peptidoglycan layer then inner membrane
What is the doubling time of most viruses?
Less than an hour
What is the doubling time of e.coli?
20-30 mins
What is the doubling time of mycobacterium lebrae?
2 weeks
What is a bacterial endotoxin?
Component of the outer membrane of bacteria eg a lipopolysaccharide in gram negative bacteria
What is a bacterial exotoxin?
Secreted proteins of gram positive and gram negative bacteria
What are bacterial free spores?
Spores formed inside a bacteria that are highly resistant to temperature and water
Give the composition, action, effect from heat, antigenecity and producer of exotoxins:
Composition: protein
Action: specific
Effect from heat: labile
Antigenicity: strong (bc protein)
Producer: gram positive and gram negative
Give the composition, action, effect from heat, antigenecity and producer of endotoxins:
Composition: lipipolysaccharide
Action: non-specific
Effect from heat: stable
Antigenicity: weak
Producer: only gram negative
How can bacteria transfer genetic information between each other?
Conjugation
How does genetic variation arise in bacteria?
Mutations (deletion, insertion, substitution)
Gene transfer (by transformation, transduction and conjugation)
What is antigenicity?
The ability of an antigen or foreign species to bind to something
What are the 2 major gram positive cocci?
Streptococci
Staphylococci
How do we differentiate streptococci and staphylococci microscopically?
Staphylococci tend to group in clusters
Streptococci tend to group in chains
What is osteomyelitis?
Infection in bone
How are staphylococci classified?
Do they contain a coagulase (blood clotting) enzyme or not
Are staphylococcus aureus and epidermis coagulase positive or negative?
Staphylococcus aureus= coagulase positive
Staphylococcus epidermis= coagulase negative
How is staphylococcus spread?
Aerosol and touch
What is MRSA?
Methicillin resistant staphylococcus aureus
What are the two ways in which staphylococcus aureus causes disease?
Pyogenic- via pus (wound infections, abscesses, pneumonia)
Toxin mediated (food poisoning, toxic shock)
What is different about coagulase-negative staphylococci?
They are opportunistic (only really affect immunocompromised or prosthetics or by going to a place they don’t belong)
What are two important coagulase negative staphylococci and what do they cause?
S. Epidermis= pusy skin
S. Saprophyticus= acute cystitis
What does alpha, beta and heamolytic negative streptococci mean?
Alpha- partial haemolysis on blood agar- green
Beta- complete lysis on blood agar- blue
Negative/gamma- no lysis
How do we tell what beta heamoytic streptococci we have?
Using Lancefield microbead agglutination test
Group A= s. Pyogenes
Group B= s.agalactiae
What infections are caused by S.pyogenes?
Respiratory (tonsillitis)
Skin and soft tissue (wound infections, cellulitis)
Scarlet fever
Complications incl rheumatic fever, glomerulonephritis
What particular complications can viridans groups streptococci cause?
Dental caries and abscesses
Infective endocarditis
What are the important aerobic gram positive bacilli?
Listeria monocytogenes (only causes infection in immunocompromised eg pregnant)
Bacillus anthracis (forms spores)
Corynebacterium diphtheriae (prevented by vaccine, leads to cvrs issues)
What are the important anaerobic gram positive bacilli?
= clostridia
C. Tetani = tetanus (from infected wounds -> muscle contractions and spasms)
C. Botulinum = botulism (from contaminated canned food -> paralysis)
C. Difficile = antibiotic associate diarrhoea -> pseudomembranous colitis (attacks gut enterocytes)
What are the features of clostridia (anaerobic gram positive bacilli)?
Spore forming
Produce toxins
What is the biggest difference between gram negative and positive bacteria?
Gram negative have an inner and outer layer
What is the lipopolysaccharide (LPS) of gram negative bacteria?
LPS= the outer leaflet of the outer membrane on gram negatives.
It comprises:
-lipid A= toxic portion
-core antigen
-somatic antigen (highly antigenic)
What are virulence determinants?
Any product/strategy that contributes to pathogenicity
1. Colonisation factors (adhesins, invasins, nutrient aquisition, defence against host)
2. Toxins (effectors)
What are family enterobacteriaceae?
= enterobacteria
Rods, mostly motile
Grow aerobically but can become anaerobic if necessary (eg large intestine = anaerobic)
What is MacConkey-lactose agar used for?
Selectively for testing enterobacteria
To see if they can use lactose for energy/food or not
For the following enterobacteria, can they use lactose, and are they motile?
Shigella flexneri
Escherichia coli (E. coli)
Salmonella enterica
Shigella flexneri cannot use lactose and is not motile
Escherichia coli (E. coli) can use lactose and is motile
Salmonella enterica cannot use lactose but is motile
What is the most common bacteria to cause of female UTIs?
E.coli- via faeces or catherisation
What are 6 common infections caused by E.coli strains?
Wound infections
UTIs
Gastroenteritis
Travellers’ diarrhoea
Bacteraemia (sometimes -> sepsis)
Meningitis sometimes in infants but rare
How can some e.coli strains become pathogenic?
There may be several ‘pathovars’
The core genome exists and can acquire pathogenic genes/accessory genes that cause pathogenicity
What is the difference between e.coli and shigella?
Shigella = “e.coli + virulence plasmid”
What are the 4 species of shigella bacteria, which is the most and least severe?
Dysenteriae (most severe)
Flexneri
Boydii
Sonnei (least severe)
What are the symptoms of shigella bacterial infections and how is it spread?
Frequent passage of stools
Pus and blood, cramps and fever
Spread person-to-person or though contaminated food and water
How does shigella cause the symptoms it does?
Induce their own uptake from M cells on the gut.
Induce apoptosis of macrophages which then release shigella when they die = inflammation and distraction of gut tissue
What are the two types of salmonella and which is responsible for the common infection?
S. Enterica = responsible for salmonellosis
S. Bongori= rare, from contact with reptiles
What are the 3 forms of salmonellosis (infection) caused by s.enterica?
Gastroenteritis (food poising from milk, poultry and eggs) (localised infection)
Enteric fever or typhoid fever (not localised= systemic) (from poor quality drinking water)
Bacteraemia
What is the route of salmonella from food/water to infection?
Invasion of gut epithelium
Transcytosed to basolateral membrane
Enters submucosa macrophages
Intracellular survival/replication
What is special about proteus mirabilis?
= pathogenic enterobacteria
Has surface motility= swarming
Is elongated &
Produces urease so urine pH increases, calcium phosphate precipitates making bladder/kidney stones
What are the features of klebsiella pneumoniae?
Evnironmental
Opportunistic- often seen in immunocompromised/elderly/neonates
Normally exists in gastrointestinal tract- here it is benign but can cause infections if goes elsewhere such as UTI, neurone, sepsis etc
This is multi drug resistance
What is a zoonosis?
Infection from an animal
What are the features of vibrio cholerae?
Facultative anaerobe
Curved rods with single polar flagellum
Causes cholera- most severe diarrhoeal disease
Contamination of drinking waster due to flooding/poor sanitation
Faecal-oral route not person-to-person
Causes production of very watery stool “rice water stool” = loss of fluids and electrolytes
What are the features of pseudomonas aeruginosa?
Free-living motile and rod shaped
Opportunistic
Resistant to many antibiotics and some disinfectants
How are pseudomonas aeruginose infections classified?
- Localised (burn/surgical wounds, UTIs keratitis- these are GREEN fluorescent)
- Systematic (bacteraemia -> sepsis) occurs in neutropenic patients- with low blood count
- ICU patients on ventilators/intubated (= ventilator acquired pneumonia)
All of these are opportunistic
What are the features of haemophilus influenzae incl what do they cause (5)?
Exclusively human parasites
Carried in the nasal pharynx- non capsulated strains
Opportunistic infections include:
Meningitis
Bronchopneumonia
Epiglottitism (caused by invasive strains with a capsule), sinusitis and otitis media
Bacteraemia (caused by invasive strains with a capsule)
Pneumonia in compromised patients (CF, COPD)
How do we diagnose (microscopically) haemophilus influenzae?
Heating a blood agar it gives a brown colour = chocolate agar
What are the features of legionella pneumophila?
Causes 1-3% of pneumonias
It is severe- has a 15-20% mortality
Affects the immunocompromised
Infection from man-made aquatic environments
What are the features of bordetella pertussis?
Pertussis= whooping cough
Short, sometimes oval, rods
Fastidious (complex nutritional needs to hard to grow in lab)
Low contagious dose- aerosol transmission
Humans are the only known reservoir
Non-invasive (localised)
What are the features of neisseria?
Non-flaggellated diplococci (called this because they go round in pairs)
Two major species: n.meningitidis and n.gonorrhoeae
Humans are the only known resevoir
What are the features of neisseria meningitidis?
= meningococcus
Carried asymptomatically by 5-10% of population
Person-to-person often when over populated groups of young people
What are the features of N.gonorrhoeae?
= gonococcus
Causes gonorrhoea- second most common STD worldwide
Person-to-person
Can be asymptomatic (10% of men, 50% of women)
Can lead to various itises
What are the features of campylobacter?
Spiral rods
Two common species: jejuni and coli
Unipolar or bipolar flagella
Most common cause of food poisoning (lives in guts of certain animals so if not cooked properly or pasteurised)
Symptoms incl mild to severe diarrhoea
What are the features of helicobacter pylori?
Spiral shaped, polar flagella tuft
Before this was discovered- we thought the stomach was sterile but this was found in about 50% of stomachs
Can cause gastritis and peptic ulcer disease
Can cause cancer (gastric adenocarcinoma)
What are the features of phylum bacteriodetes?
Non-motile rods
Most abundant bacteria in large intestine
Opportunistic (eg through ulcers)
Most common cause of anaerobic infections
Main one is B.Fragilis (least common but causes most infections)
What are the features of phylum chlamydiae?
Very small non-motile
Not rod shaped or spiral shaped!
Obligate intracellular parasites
Many live asymptomatically
Can only be detected by PCR or by seeing if the person has antibodies- though they could have had these for years
What is the life-cycle of chlamydia?
Unique growth cycle with 2 developmental stages:
1. Elementary Bodies (rigid) which enter cells through endocytosis. They then differentiate into…
2. Reticulate bodies (fragile) which replicate and acquire nutrients from host cell
What are the 3 important members of the Chlamydia genus?
C. Trachomatis
C. Pneumoniae
C. Psittaci
What are the strains of Chlamydia Trachomatis?
There are 3 strains:
Trachoma biovar (can lead to blindness, through eye-to-eye transmission)
Genital tract biovar (most common STD= what we know as chlamydia) (infects epithelial cells and can ascend to uterus and ovaries) (can cause conjunctivitis from hand-to-eye transmission)
Lympho granuloma venereum biovar
What are the stages of caring out a gram stain?
- Fresh culture must be used
- Dilute cells and form a thin film over the slide
- Pass slide over a Bunsen burner to make it warm (not hot!)
- Stain cells with crystal violet then rinse with water after 30-40 secs
- Add grams iodine and leave for 1 minute before rinsing
- Decolorise the cells with iodine or ethanol (dropwise with slide tilted) then wash off excess
- Cover cells with safronin and then rinse with water before drying
What are the different shapes of virus?
Helical
Isoahedral
Complex
Non-enveloped
Enveloped
What is a virus?
Infectious, obligate intracellular parasite comprising genetic material (DNA OR RNA surrounded by a protein coat and/or membrane
How do viruses replicate?
- Attachment to a specific receptor
- Cell entry: uncoating of virion within cell
- Host cell interaction + replication (migration of genome to nucleus and transcription to mRNA using host materials, translation of mRNA produces structural proteins, viral genome and non-structural proteins such as enzymes)
- Assembly of virion (= complete infectious viral particle)
- Release of new virus particles
How do viruses cause disease (5 ways) ?
- Direct distraction of host cells
- Modification of host cell
- Over-reactivity of immune system
- Damage through cell proliferation
- Evasion of host defences (at cellular level and at molecular level)
How does poliovirus cause disease?
By direct destruction of host cells
Causes lysis of Neurons -> paralysis
How does rotavirus cause disease?
By modification of host cells
Causes atrophies in villi and flatten epithelial cells to decrease small intestine surface area so fewer nutrients are absorbed
Causes hyperosmotic state
Causes profuse diarrhoea
How does hepatitis B cause disease?
By over-reactivity of immune system
Produces cytotoxic response which leads to jaundice, fever etc
How does covid 19 cause disease?
By over-activity of immune system
How does human papilloma virus cause disease and what disease does it cause?
Causes cervical cancer
By damage though cell proliferation
(Viral expression of HPV proteins + viral DNA is integrated into host chromosomes leads to dysplasia and neoplasia)
Give an example for each way viruses can cause disease?
- Direct distraction of host cells (poliovirus)
- Modification of host cell (rotavirus)
- Over-reactivity of immune system (hep B)
- Damage through cell proliferation (papilloma)
- Evasion of host defences (cellular level =herpesviridae) (molecular level = HIV, influenza)
How can viruses evade host defences?
At a molecular level -> antigenic variability, prevention of host cell apoptosis, down regulation of proteins, interference with host cell antigen processing pathways eg. HIV
What are important things to ask a mother at their 6 week post-natal check up?
Ask about their lochia (bleeding after birth)
Ask about contraception
Ask about support/partner
Ask about mental health
Ask about domestic abuse
Check for baby genital mutilation
Ask any other concerns
Do baby check
What do you do in a baby check?
Red reflex (using ophthalmoscope)
Hip dysplasia
Check ears (too low -> down’s)
Check testicular descention
Check heart
List what is screened for antenatally?
Fetal anatomy scan
Screening for down’s
Sickle cell and thalassaemia
Screening for infectious diseases
What is screened for in a newborn baby?
Physical external inspection
Hearing test
Newborn blood spot = CF, PKU, sickle cell etc
Physical examination = cardiac, hip dysplasia, eyes, testes
What is screened for at the 6 week baby check?
Physical = heart, hips, cataract, testes
Includes = weight, head circumference, appearance, tone/movement/posture, head and eyes
What is reviewed by schools for children age 5 ish years?
Height
Weight
Vision
Hearing
What is reviewed by the health visitor at 2-2.5 yrs?
General development
Growth, eating and activity
Tooth brushing/dental appointments
Behaviour
Sleep
Safety
Vaccinations
What are the ways in which we can obtain passive immunity?
(Antigens are provided directly to us)
Mostly cross-placental
Sometimes via transfusion of blood/serum
What are the types of vaccines (or things they can be made from)?
Made from inactivated virus
Attenuated live organism
Secreted products
Constituents of cell walls
Recombinant components
What is primary and secondary vaccine failure?
Primary vaccine failure= person doesn’t develop immunity
Secondary= initially responds but protection wanes over time
What are 6 examples of major vaccine preventable diseases?
Diptheria
Polio
Tetanus
Pertussis (= whooping cough)
Haemophilus influenza type B
Meningococcal disease (-> meningitis, sepsis)
What are signs of respiratory distress in babies?
Breathing very quickly (infants should breath at 30-50- more when they’re younger)
Prominent ribs and sub costal recession because diaphragm is trying so hard
What does polio do to cause disease?
Attacks the nerves causing poliomyelitis (damage to myelin)
When the nerves are damaged, the muscles begin to waste = muscle atrophy
What reasons could a disease be notifiable for?
They’re very dangerous/harmful
Very infectious and vaccine preventable
If they need specific control measures
Name the sterile sites on the body (6) ?
Blood
CSF
Joints
Lower resp tract
Pleural fluid
Peritoneal cavity
Name the sites of the body colonised with flora (bacteria) (6):
Gastrointestinal tract
Skin
Bladder
Oral cavity
Vagina
Urethra
What are the symptoms of scarlet fever?
“Sandpaper rash” = rash feels rough
“Strawberry tongue”
Think of risk settings and co-inections
Define adrenergic:
Relating to adrenaline or noradrenaline and their receptors
Define cholinergic:
Relating to acetylcholine and its receptors
What are the differences between somatic and autonomic nervous system?
Somatic= single neuron, innervates skeletal muscles, leads to excitation
Autonomic= tow neuron chain- two neurones separated by autonomic ganglion, smooth muscle & cardiac muscles & glands, leads to either excitation or inhibition
In general, what are the receptors and neuro-transmitters pre and post-ganglionic?
Preganglionic= ACh acts on NICOTINIC receptors
Postganglionic= ACh acts on MUSCARINIC receptors (parasympathetic) and NORADRENALINE acts on Alpha and Beta receptors (sympathetic)
What are the cranial nerves inner sting the parasympathetic nuclei of the brainstem?
3
7
9
10
What are the exceptions for pre and post-ganglion in neurotransmitters?
Sometimes ACh is released at sympathetic post-ganglion if terminals (eg in sweat glands)
Nitric oxide is released from parasympathetic postganglionic termini in blood vessels
What are the 5 types of muscarinic receptors?
M1: brain
M2: heart
M3: all organs with parasympathetic innervation
M4: mainly CNS
M5: mainly CNS
All found outside the cell and will activate intracellular processes though G-proteins
What are the M2 muscarinic receptors- what happens when it is activated?
On the heart sino-atrial node (pacemaker)
Activation decreases the heart rate
On the atrio-ventricular node
Decreases conduction velocity (slows down heart)
Induces AV node block (PR interval increases)
What are the M3 muscarinic receptors and what happens when they are activated?
In the resp system:
Acivation produces mucus and smooth muscle contraction (leading to bronchoconstriction)
In the GI tract:
Increases saliva production and gut motility
Stimulates biliary secretion
In the skin- only in places were SYMPathetic system releases ACh
Activation causes sweating
In the urinary system:
Activation causes contraction of detrusor muscle and relaxation of internal urethral sphincter so urination
In the eye:
Causes myosis (pupil constriction)
Causes increased drainage of aqueous humours and secretion of tears
What does activation of M3 muscarinic receptors in the respiratory system do?
Acivation produces mucus and smooth muscle contraction (leading to bronchoconstriction)
What does activation of M3 muscarinic receptors in the GI tract do?
Increases saliva production and gut motility
Stimulates biliary secretion
What does activation of M3 muscarinic receptors in the skin do- and where in the skin are they ?
Only in places where there is sympathetic release of ACh
Causes sweating
What does activation of M3 muscarinic receptors in the urinary system do?
Contraction of detrusor muscle
Relaxation of internal urethral sphincter
= urination
What does activation of M3 muscarinic receptors in the eye cause?
Myosis (constriction of pupils)
Increased drainage of aqueous humours
Secretion of tears
What would be observed in muscarinic poisoning?
Myosis and blurred vision
Hypersalivation
Bronchoconstriction
Bradycardia/ heart block
Diarrhoea
Polyuria (too much urine)
Hyperhidrosis (excessive sweating)
What are pilocarpine eye drops, what do they target and how do they work?
They are M3 agonists (= do what M3 does)
They increase drainage of aqueous humour, reduce ocular pressure and treat closed angle glaucoma (which occur when fluid is trapped)
Also can treat dry mouth
